Potential Treatments for COVID-19; a Narrative Literature Review.

SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11th. There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.


Introduction
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a newly emerging human infectious coronavirus, originated in Wuhan, China, and has been spreading rapidly in China and other countries since December 2019 (1). The World Health Organization (WHO) also declared a global emergency on January 31 s t due to increasing concerns over its fast spread, and on March 11 t h the disease was recognized as a pandemic. Since the bases for pathogenesis of this virus and its proliferation is unclear, there is still no vaccine or definitive treatment against it. Thus, medications used against SARS-CoV-2 are mainly based on their effectiveness on earlier strains of coronavirus, SARS-CoV and MERS-CoV. Therefore, the immediate introduction of potential COVID-19 treatments can be essential and salvaging. In this article, new potential COVID-19 therapies are briefly reviewed.

Clinical reports
Clinical reports on COVID-19 treatment mainly described empirical treatments and clinical experiences during its treatment. In 2020, Gao et al. studied the effect of chloroquine and hydroxychloroquine in treatment of COVID-19 in over 100 patients and 10 hospitals in Wuhan, Jingzhou, Guangzhou, Beijing, Shanghai, Chongqing, and Ningbo. The results of this study showed that chloroquine phosphate is effective in preventing the exacerbations of pneumonia, decreasing lung involvements in imaging findings, promoting a virus-negative conversion and shortening the disease course. In addition, there were no serious adverse effects observed at therapeutic doses (2). Also, according to Jian-ya et al., treatment of 51 COVID-19 patients with traditional Chinese medicine, interferon, Lopinavir, Ritonavir and short-term (3 to 5 days) corticosteroids was successful and resulted in recovery and discharge of 50 patients (3). Qin et al. also reported that administration of moxifloxacin, lopinavir, and interferon to non-ICU patients and the addition of methylprednisolone to the above treatment for ICU patients resulted in 26 patients being discharged from intensive care unit (ICU) and 16 patients being discharged from hospital (4). Also, Zhou et al. reported that short-term moderate-dose corticosteroid (160 mg/day) plus immunoglobulin (20 g/day) significantly reduced lung injury, normalized lymphocyte counts, body temperature, Creactive protein levels, and oxygenation index in 10 COVID-19 patients (5). On the other hand, while studying 416 COVID-19 patients, Shang et al. reported that corticosteroid therapy and gamma globulin administration increased mortality and appeared to be useful only in patients with lower lymphocyte counts (6). According to the mentioned clinical reports, the administration of corticosteroids for COVID-19 patients is still questionable.

Case reports
So far, there are three published case reports on the successful treatment of patients with COVID-19. In the first report Lim et al. described a 54-year-old man with COVID-19 who was treated with Lopinavir/Ritonavir from day 10 of ill-ness, 2 tablets (Lopinavir 200mg / Ritonavir 50mg) every 12 hours. Since first day of administration, β-coronavirus viral load started to decrease, and little or no detectable coronavirus titers have been observed since then (7). In another case report, Zhang et al. described a couple who were both 38 years old and were suffering from COVID-19. Their treatment included Methylprednisolone 40 mg daily intravenous (IV) injections for one and five days for the male and the female patient respectively, human gamma globulin 10g IV qd for five and seven successive days for the male and the female patient, respectively, and then the dose was changed to 5g for both of them, in addition to Moxifloxacin, Oseltamivir, Arbidol hydrochloride, and Tanreqing (Chinese patent medicine). After 11 days, the female patient and after 14 days the male patient recovered with regards to inflammatory factors and were discharged from the hospital (8).
In the third case report, Chen et al. reported a 45-year-old woman with COVID-19 and stated that after treatment with Thalidomide (100 mg orally once a day) and Methylprednisolone (40 mg intravenously bid for 3 days then reduced to once a day for 5 days) the overall patient status was improved, oxygen index was increased, symptoms of nausea and vomiting were alleviated, and cytokine levels were decreased (9).

Potential drugs
Several articles have suggested medicines, potentially effective for the treatment of COVID-19 ( Table 1). Most of these suggestions are based on in vitro studies, virtual screenings and records of their effects on SARS and MERS. In addition to these medications, Tocilizumab has recently been suggested as a COVID-19 treatment. Studies have shown that IL-6 levels significantly correlated with the severity of COVID-19, C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer levels and T cell counts, and it has been suggested that Tocilizumab, with its inhibitory effect on IL-6, may be effective in treatment of COVID-19 (10,11). However, no clinical study has demonstrated the effects of Tocilizumab on COVID-19 and further studies are indeed required.

Conclusion
Apparently, in addition to the drugs currently prescribed to treat COVID-19, Arbidol hydrochloride, interferon, and Thalidomide plus Methylprednisolone can also be used due to their effects reported in clinical studies. However, more studies are needed to confirm the use of corticosteroids, as there are conflicting reports regarding their efficacy. Also, potential drugs listed in Table 1, such as Remdesivir, Atazanavir, Saquinavir, and Formoterol, and Tocilizumab can be introduced as treatments for COVID-19 if they prove to be effective in animal and clinical studies.

Funding Support
None.

Conflict of Interest
None.